Though current vaccines reduce the impact of influenza, IAV remains a major human pathogen with an enormous global and domestic impact, causing 30,000 deaths and economic costs totaling tens of billions dollars each year in the USA. Despite its remarkable impact on public health, we have only a limited understanding of the molecular mechanisms underlying viral pathogenesis and its ability to evade the immune response. In this project we are studying a number of aspects of the interaction between IAV and the host. Most of studies utilize the mouse model of infection. Our interests include understanding selection of antigenic variants in vivo, host-pathogen interactions in regulating anti-viral immunity, and the role of the PB1-F2 protein in viral pathogenesis. We found that PB1-F2 enhances influenza A virus pathology and are investigating its mechanism of action and additional roles it may play during influenza virus infection.